Sodium metabolism and disorders

Dr Manik Kataruka

Physiology

• Sodium is the major extracellular cation- 135-145mmol/lt.

• The total body sodium content of 70kg male subject is of 4000 mmol.

• 50% of total body sodium content exists in the extracellular compartment.

• 40-45% is found in bone, skin and cartilage. • 5-10% occurring intracellularly. • The average dietary sodium intake - 150 mmol.

INTERSTITIAL vs PLASMA SODIUM

• The extracellular space is subdivided into the intravascular compartment and the interstitial compartment.

• Water moves freely across both the compartment.

• The ionic composition of two compartments is not identical, because of (a) a difference in protein concentration (b) the Gibbs-Donnan effect.

Contd.

• Exchangeable sodium- 70% of total sodium, both intra and extra cellular and part of bone sodium.

• Non exchangeable sodium- bone, cartilage and skin.

• The sodium concentration of cartilage is nearly twice that of plasma.

• Proteoglycans in skin,bone serve as a sodium reservoir.

Edelman equation

• High salt diet accumulation of Na in skin interstitium activation of tonicity responsive enhancer binding protein (TonEBP) in mononuclear phagocyte system (MPS) cells vascular endothelial growth factor-C secretion by macrophages increased endothelial nitric oxide synthase (eNOS) expression.

• Inhibition of these , increases blood pressure.

RENAL REGULATION OF SODIUM EXCRETION

• Each day, the glomeruli filter roughly 25,000 mEq of Na.

• Kidneys typically absorb over 99%.• Rates of Na reabsorption are greatest in the

proximal tubule.• The ability to alter Na transport in the proximal

tubule is limited, and highest in collecting duct.

Overview of Na+ Reabsorption along the Nephron

65% of filtered Na+ is reabsorbed from the proximal tubule.25% of filtered Na+ is reabsorbed from the thick ascending limb.5% of filtered Na+ is reabsorbed from the distal tubule.4-5% of filtered Na+ is reabsorbed from the collecting duct.

Proximal Tubule: Na+ Reabsorption

Thick Ascending Limb

DCT and CNT

body sodium balance

Sensors mechanism

Effectors for control of sodium balance: the KIDNEY

Renal sodium regulation

Tubuloglomerular feedback

• Changes in tubular fluid Na+ inversely affect GFR.

• Uptake of salt by NKCC2 ATP release broken down to adenosine afferent arteriolar constriction.

Peritubular capillary starling forces

•Rate is the absolute rate of reabsorption.

•Kr is the capillary reabsorption coefficient.

•πc and Pc are the local capillary oncotic and hydraulic pressures, and πi and Pi are the corresponding interstitial pressures.

Pressure natriuresis• Renal Na+ and water

excretion are increased when renal arterial pressure increases without change in GFR

• Mechanism is intra-renal and does not require neural or endocrine input

Effect of sympathetic nervous system

Aldosterone

• Alters renal Na+ reabsorption in response to dietary fluctuations

• Main stimuli for release: Angiotensin II, hyperkalemia, ACTH

• Main effect: Increases number of open luminal Na+ channels and activity and number of basolateral Na+-K+ ATPase pumps in principal cells of collecting ducts

Angiotensin II

• Efferent > afferent arteriolar constriction (increased FF) results in changes in peritubular Starling forces that facilitate Na+ reabsorption

• Direct stimulation of Na+-H+ antiporter in proximal tubules

• Stimulates aldosterone secretion from adrenal glands

Atrial natriuretic peptide

prostaglandins

HYPONATREMIA

Hyponatremia

• Serum sodium concentration <135 mmol/L.• 15–20 % of emergency admissions to hospital.• Mild- 130-135 mmol/L• Mod- 125-129 mmol/L• Severe- <125 mmol/L• Acute- <48 hrs• Chronic- >48hrs

Etiology

Causes of non-hypotonic hyponatremia

Criteria for diagnosis of SIADH

Differences between SIADH and cerebral salt wasting

Symptoms of hyponatremia

GENERAL GUIDELINES• Na deficit = 0.6 x wt(kg) x (desired [Na] - actual [Na])

• When do we need to Rx quickly?– Acute (<24h) severe (< 120 mEq/L) Hyponatremia

• Prevent brain swelling or Rx brain swelling– Symptomatic Hyponatremia (Seizures, coma, etc.)

• Alleviate symptoms

• Initially treat“Quickly”: 3% NS, 1 mEq/kg/h until:• Symptoms stop• 3-4h elapsed and/or Serum Na has reached 120 mEq/L

• Then 0.5 mEq/L/h with 0.9% NS or simply fluid restriction.

• Aim for overall 24h correction to be < 10-12 mEq/L/d to prevent myelinolysis

ADROGUE MADIAS FORMULA

• Calculating volume of infusate

Volume of infusate = {1000 mL x (Change in[Na+])goal}/(Change in [Na+])

• Calculating rate of infusion

Rate of infusion = volume of infusate/hours of infusion

• Patient’s weightX desired correction rate(mEq/L/hr)= infusion rate of 3% NaCl(ml/hr)

Chronic asymtomatic hyponatremia

• Stop non-essential fluids, medications.• Cause-specific treatment.• Fluid restriction.• In moderate hyponatraemia- increase in serum

sodium >10 mmol/L during the first 24 h and >8 mmol/L during every 24 h thereafter.

SIADH

• Severe hyponatremia with hypertonic saline.• Fluid restriction- 0.5- 1 Lt per day.• Demeclocycline• Urea• Vaptans

Karen E. Yeates, Michael Singer, CMAJ • FEB. 3, 2004; 170 (3)

VAPTANS• Vasopressin receptor antagonists.• Use in euvolemic/hypervolemic hyponatremia.• Not suitable for hyponatremia due to cerebral

salt wasting and psychogenic polydipsia.• Approved for patient with serum Na

<125mEq/L or >125mEq/L with symptoms of hyponatremia and resistant to fluid restriction.

• Avoided in pregnant women.

• Aquaresis delayed 1-2 h.

• Promotes slow aquaresis.

• Not useful if Sr Cr is >2.5mg/dl.

• Adverse Effects: -– Thirst 8-16%; dry mouth 4-13%

– Hypernatremia in 5%

Hypernatremia

• Serum Na> 145mEq/l• Hypertonic, hyperosmolar.• 1% of hospitalised patients.• Free water loss is the major cause.

Clinical feature

Osmolality (mOsm/kg) Manifestations

350–375 Restlessness, irritability

375–400 Tremulousness, ataxia

400–430 Hyperreflexia, twitching, spasticity

>430 Seizures and death

Effects of Hypernatremia on the Brain and Adaptive Responses.

Etiology

•Point prevalence of hyponatremia was 13.5% and of hypernatremia was 2%.•During follow-up of ~5 years, 26% patients developed at least one episode of hyponatremia and 7% had hypernatremia

Thank you